US12018272B2ActiveUtilityA1

RNA-guided human genome engineering

98
Assignee: HARVARD COLLEGEPriority: Dec 17, 2012Filed: Apr 6, 2023Granted: Jun 25, 2024
Est. expiryDec 17, 2032(~6.4 yrs left)· nominal 20-yr term from priority
C12N 15/11C12N 15/79C12N 15/113C12N 5/10C12N 15/85A61K 48/00C12N 2800/80C12Y 301/00C12N 9/22C12N 15/1024C12N 2810/55C12N 15/907C12N 15/87C12N 15/8201C12N 15/81C12N 15/01C12N 15/90C12N 15/63C12N 15/102C12N 2310/20C12N 15/10
98
PatentIndex Score
2
Cited by
246
References
17
Claims

Abstract

A method of altering a eukaryotic cell is provided including transfecting the eukaryotic cell with a nucleic acid encoding RNA complementary to genomic DNA of the eukaryotic cell, transfecting the eukaryotic cell with a nucleic acid encoding an enzyme that interacts with the RNA and cleaves the genomic DNA in a site specific manner, wherein the cell expresses the RNA and the enzyme, the RNA binds to complementary genomic DNA and the enzyme cleaves the genomic DNA in a site specific manner.

Claims

exact text as granted — not AI-modified
The invention claimed is: 
     
       1. An ex vivo human cell comprising:
 a Cas9 protein complexed with an RNA, 
 wherein the RNA comprises the sequence 
 
       
         
           
                 
               
                   (SEQ ID NO: 46) 
                 
                   GUUUUAGAGCUAGAAAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAAC 
                 
                     
                 
                   UUGAAAAAGUGGCACCGAGUCGGUGC. 
                 
             
                
                
                
                
               
            
           
         
       
     
     
       2. The ex vivo human cell of  claim 1 , wherein the Cas9 protein is an  S. pyogenes  Cas9 protein. 
     
     
       3. The ex vivo human cell of  claim 1 , wherein the RNA is about 100 nucleotides in length. 
     
     
       4. The ex vivo human cell of  claim 1 , wherein the RNA is complementary to a target nucleic acid sequence within the ex vivo human cell. 
     
     
       5. The ex vivo human cell of  claim 4 , wherein the RNA is hybridized to the target nucleic acid sequence in the ex vivo human cell. 
     
     
       6. The ex vivo human cell of  claim 1 , wherein the RNA has a secondary structure comprising a first hairpin and a second 3′ hairpin. 
     
     
       7. An ex vivo human cell comprising:
 a Cas9 protein complexed with an RNA, 
 wherein the RNA comprises the sequence 
 
       
         
           
                 
               
                   (SEQ ID NO: 46) 
                 
                   GUUUUAGAGCUAGAAAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAAC 
                 
                     
                 
                   UUGAAAAAGUGGCACCGAGUCGGUGC,  
                 
                   and 
                 
             
                
                
                
                
                
               
            
           
         
         wherein the Cas9 protein bears an SV40 nuclear localization signal. 
       
     
     
       8. The ex vivo human cell of  claim 7 , wherein the SV40 nuclear localization signal is at a C-terminus of the Cas9 protein. 
     
     
       9. The ex vivo human cell of  claim 7 , wherein the Cas9 protein is an  S. pyogenes  Cas9 protein. 
     
     
       10. The ex vivo human cell of  claim 7 , wherein the RNA is about 100 nucleotides in length. 
     
     
       11. The ex vivo human cell of  claim 7 , wherein the RNA is complementary to a target nucleic acid sequence within the ex vivo human cell. 
     
     
       12. The ex vivo human cell of  claim 11 , wherein the RNA is hybridized to the target nucleic acid sequence in the ex vivo human cell. 
     
     
       13. The ex vivo human cell of  claim 7 , wherein the RNA has a secondary structure comprising a first hairpin and a second 3′ hairpin. 
     
     
       14. An ex vivo human cell comprising:
 a Cas9 protein complexed with an RNA, 
 wherein: 
 the RNA comprises the sequence 
 
       
         
           
                 
               
                   (SEQ ID NO: 46) 
                 
                   GUUUUAGAGCUAGAAAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAAC 
                 
                     
                 
                   UUGAAAAAGUGGCACCGAGUCGGUGC,  
                 
                   and 
                 
             
                
                
                
                
                
               
            
           
         
         the RNA is at least 100 nucleotides in length. 
       
     
     
       15. The ex vivo human cell of  claim 14 , wherein the RNA is complementary to a target nucleic acid sequence within the ex vivo human cell. 
     
     
       16. An ex vivo human cell comprising:
 an  S. pyogenes  Cas9 protein complexed with an RNA, 
 wherein: 
 the RNA comprises the sequence 
 
       
         
           
                 
               
                   (SEQ ID NO: 46) 
                 
                   GUUUUAGAGCUAGAAAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAAC 
                 
                     
                 
                   UUGAAAAAGUGGCACCGAGUCGGUGC, 
                 
             
                
                
                
                
               
            
           
         
         the RNA is at least 100 nucleotides in length, and 
         the  S. pyogenes  Cas9 protein bears a SV40 nuclear localization signal at a C-terminus of the  S. pyogenes  Cas9 protein. 
       
     
     
       17. The ex vivo human cell of  claim 16 , wherein the RNA is complementary to a target nucleic acid sequence within the ex vivo human cell.

Cited by (0)

No later patents cite this yet.

References (0)

No backward citations on record.